NPASS Compound

Natural Product: NPC104138

Natural Product ID	NPC104138
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	(2E,4E)-N-Isobutyleicosa-2,4-Dienamide
IUPAC Name	(2E,4E)-N-(2-methylpropyl)icosa-2,4-dienamide
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL2347638
PubChem CID	6441067
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000012] Lipids and lipid-like molecules [CHEMONTID:0003909] Fatty Acyls [CHEMONTID:0000331] Fatty amides [CHEMONTID:0001096] N-acyl amines

The Chemical Classification was calculated by Classyfire, a software for chemical taxonomy calculation. Reference: DOI:10.1186/s13321-016-0174-y.

Chemical Representations

RDKit 3D 71 70 0 0 0 0 0 0 0 0999 V2000 9.9517 1.7840 0.0961 C 0 0 0 0 0 0 0 0 0 0 0 0 8.6932 2.1752 0.8446 C 0 0 0 0 0 0 0 0 0 0 0 0 7.5803 2.3143 -0.1714 C 0 0 0 0 0 0 0 0 0 0 0 0 6.2896 2.7161 0.4814 C 0 0 0 0 0 0 0 0 0 0 0 0 5.7729 1.7667 1.5054 C 0 0 0 0 0 0 0 0 0 0 0 0 5.4853 0.3846 1.0423 C 0 0 0 0 0 0 0 0 0 0 0 0 4.4528 0.2918 -0.0566 C 0 0 0 0 0 0 0 0 0 0 0 0 4.2917 -1.1842 -0.3796 C 0 0 0 0 0 0 0 0 0 0 0 0 3.2799 -1.4367 -1.4737 C 0 0 0 0 0 0 0 0 0 0 0 0 1.9100 -0.9298 -1.1069 C 0 0 0 0 0 0 0 0 0 0 0 0 1.3569 -1.5674 0.1310 C 0 0 0 0 0 0 0 0 0 0 0 0 1.1740 -3.0216 0.1004 C 0 0 0 0 0 0 0 0 0 0 0 0 0.3323 -3.6901 -0.8903 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.1009 -3.4425 -1.0155 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.5387 -2.0844 -1.4367 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.0668 -2.1124 -1.4540 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.7379 -1.2892 -0.6747 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.1706 -1.1921 -0.5704 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.7029 -0.3171 0.2546 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.1465 -0.1276 0.4463 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.5079 0.7498 1.2707 N 0 0 0 0 0 0 0 0 0 0 0 0 -8.8135 1.1130 1.6187 C 0 0 0 0 0 0 0 0 0 0 0 0 -9.4144 2.1327 0.7113 C 0 0 0 0 0 0 0 0 0 0 0 0 -9.5230 1.6278 -0.6972 C 0 0 0 0 0 0 0 0 0 0 0 0 -8.4354 3.3287 0.7053 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.9965 -0.9202 -0.2817 O 0 0 0 0 0 0 0 0 0 0 0 0 9.7383 1.2745 -0.8671 H 0 0 0 0 0 0 0 0 0 0 0 0 10.5652 2.6958 -0.1411 H 0 0 0 0 0 0 0 0 0 0 0 0 10.5203 1.0703 0.7262 H 0 0 0 0 0 0 0 0 0 0 0 0 8.4724 1.3833 1.5850 H 0 0 0 0 0 0 0 0 0 0 0 0 8.8589 3.1151 1.3714 H 0 0 0 0 0 0 0 0 0 0 0 0 7.5144 1.4633 -0.8399 H 0 0 0 0 0 0 0 0 0 0 0 0 7.8772 3.1935 -0.8285 H 0 0 0 0 0 0 0 0 0 0 0 0 6.4941 3.6854 1.0194 H 0 0 0 0 0 0 0 0 0 0 0 0 5.5195 2.9227 -0.2959 H 0 0 0 0 0 0 0 0 0 0 0 0 6.4526 1.6860 2.3823 H 0 0 0 0 0 0 0 0 0 0 0 0 4.8133 2.1952 1.9025 H 0 0 0 0 0 0 0 0 0 0 0 0 5.1548 -0.1967 1.9463 H 0 0 0 0 0 0 0 0 0 0 0 0 6.4009 -0.1429 0.6811 H 0 0 0 0 0 0 0 0 0 0 0 0 3.5292 0.7596 0.3215 H 0 0 0 0 0 0 0 0 0 0 0 0 4.8202 0.7667 -0.9894 H 0 0 0 0 0 0 0 0 0 0 0 0 4.0293 -1.6864 0.5743 H 0 0 0 0 0 0 0 0 0 0 0 0 5.2791 -1.5629 -0.6988 H 0 0 0 0 0 0 0 0 0 0 0 0 3.3143 -2.4964 -1.7433 H 0 0 0 0 0 0 0 0 0 0 0 0 3.6258 -0.8588 -2.3582 H 0 0 0 0 0 0 0 0 0 0 0 0 1.2373 -1.0369 -1.9564 H 0 0 0 0 0 0 0 0 0 0 0 0 2.0195 0.1574 -0.9187 H 0 0 0 0 0 0 0 0 0 0 0 0 0.4649 -1.0363 0.4635 H 0 0 0 0 0 0 0 0 0 0 0 0 2.0887 -1.3660 0.9969 H 0 0 0 0 0 0 0 0 0 0 0 0 2.1836 -3.5738 0.1815 H 0 0 0 0 0 0 0 0 0 0 0 0 0.7313 -3.2973 1.1318 H 0 0 0 0 0 0 0 0 0 0 0 0 0.7662 -3.6106 -1.9436 H 0 0 0 0 0 0 0 0 0 0 0 0 0.4482 -4.8228 -0.7014 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.4704 -4.1352 -1.8542 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.6932 -3.7848 -0.1091 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.2374 -1.2586 -0.8288 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.2936 -1.9805 -2.5274 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.5919 -2.7839 -2.0806 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.1305 -0.6193 -0.0493 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.7904 -1.8358 -1.1657 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.0333 0.3037 0.8374 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.7613 1.5862 2.6657 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.5306 0.2591 1.6911 H 0 0 0 0 0 0 0 0 0 0 0 0 -10.3996 2.4694 1.1060 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.5500 1.5730 -1.1828 H 0 0 0 0 0 0 0 0 0 0 0 0 -10.1693 2.3764 -1.2666 H 0 0 0 0 0 0 0 0 0 0 0 0 -10.0723 0.6566 -0.7397 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.7743 3.9391 -0.1525 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.5281 3.8003 1.6851 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.4330 2.9051 0.5821 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.8759 -1.2212 0.1475 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 1 0 3 4 1 0 4 5 1 0 5 6 1 0 6 7 1 0 7 8 1 0 8 9 1 0 9 10 1 0 10 11 1 0 11 12 1 0 12 13 1 0 13 14 1 0 14 15 1 0 15 16 1 0 16 17 2 0 17 18 1 0 18 19 2 0 19 20 1 0 20 21 2 0 21 22 1 0 22 23 1 0 23 24 1 0 23 25 1 0 20 26 1 0 1 27 1 0 1 28 1 0 1 29 1 0 2 30 1 0 2 31 1 0 3 32 1 0 3 33 1 0 4 34 1 0 4 35 1 0 5 36 1 0 5 37 1 0 6 38 1 0 6 39 1 0 7 40 1 0 7 41 1 0 8 42 1 0 8 43 1 0 9 44 1 0 9 45 1 0 10 46 1 0 10 47 1 0 11 48 1 0 11 49 1 0 12 50 1 0 12 51 1 0 13 52 1 0 13 53 1 0 14 54 1 0 14 55 1 0 15 56 1 0 15 57 1 0 16 58 1 0 17 59 1 0 18 60 1 0 19 61 1 0 22 62 1 0 22 63 1 0 23 64 1 0 24 65 1 0 24 66 1 0 24 67 1 0 25 68 1 0 25 69 1 0 25 70 1 0 26 71 1 0 M END

Standard InCHIKey	LMZPUHBJSQVRHE-HYGARKJASA-N
Standard InCHI	InChI=1S/C24H45NO/c1-4-5-6-7-8-9-10-11-12-13-14-15-16-17-18-19-20-21-24(26)25-22-23(2)3/h18-21,23H,4-17,22H2,1-3H3,(H,25,26)/b19-18+,21-20+
SMILES	CCCCCCCCCCCCCCC/C=C/C=C/C(=NCC(C)C)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	363.35	Volume:	435.538 ? Van der Waals volume.
Dense:	0.834	LogP:	7.838 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	4.262 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-5.49 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	18.0	Rigid Bonds:	3.0
TPSA:	32.59 ? Topological Polar Surface Area.	H-Bond Acceptor:	2.0
H-Bond Donor:	1.0	Rings:	0.0
Heavy Atoms:	2.0

MedChem Properties

QED Drug-Likeness Score:	0.113	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	2.792	Fsp³:	0.792
MCE-18:	0.0 ? MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.	Lipinski Rule-of-5:	Rejected
Pfizer Rule:	Accepted	GSK Rule:	Accepted
Golden Triangle Rule:	Rejected	BMS Rule:	1
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.682	Fluc inhibitor:	0.635 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.002 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.1 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.452	Promiscuous compounds:	0.061

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.025	MDCK Permeability:	-4.786
Pgp-inhibitor:	0.026	Pgp-substrate:	0.08
PAMPA:	0.0 ? The experimental data for Peff was logarithmically transformed (logPeff). Molecules with log Peff values below 2.0 were classified as low-permeability (Category 0), while those with log Peff values exceeding 2.5 were classified as high-permeability (Category 1).	Human Intestinal Absorption (HIA):	0.243
20% Bioavailability (F20%):	0.931	30% Bioavailability (F30%):	0.999
50% Bioavailability (F50%):	0.997

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.0	MRP1:	0.606
Plasma Protein Binding (PPB):	98.633%	Volume Distribution (VD):	0.685
Fu:	1.041% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.955
OATP1B3 inhibitor:	1.0	BCRP inhibitor:	0.655
BSEP inhibitor:	0.999

ADMET: Metabolism

CYP1A2-inhibitor:	0.253	CYP1A2-substrate:	0.999
CYP2C19-inhibitor:	0.864	CYP2C19-substrate:	0.988
CYP2C9-inhibitor:	0.629	CYP2C9-substrate:	0.981
CYP2D6-inhibitor:	0.713	CYP2D6-substrate:	0.284
CYP3A4-inhibitor:	0.934	CYP3A4-substrate:	1.0
CYP2B6-substrate:	0.089	CYP2C8-inhibitor:	1.0
HLM stability:	0.218 ? Human liver microsomal (HLM) stability. Category 0: stable+ (HLM > 30 min); Category 1: unstable- (HLM ≤ 30 min). The output value is the probability of human liver microsomal instability, where a value closer to 1 indicates a higher likelihood of instability.

ADMET: Excretion

Clearance (CL):

5.42

Half-life (T1/2):

0.578

ADMET: Toxicity

hERG Blockers:	0.405	hERG Blockers (10um):	0.601
Human Hepatotoxicity (H-HT):	0.926	Drug-induced Liver Injury (DILI):	0.728
AMES Toxicity:	0.414	Rat Oral Acute Toxicity:	0.339
Maximum Recommended Daily Dose:	0.366	Skin Sensitization:	0.999
Carcinogencity:	0.677	Eye Corrosion:	0.262
Eye Irritation:	0.966	Respiratory Toxicity:	0.969
Drug-induced Neurotoxicity:	0.064	Ototoxicity:	0.387
Hematotoxicity:	0.217	Drug-induced Nephrotoxicity:	0.704
Genotoxicity:	0.0	RPMI-8226 Immunitoxicity:	0.022
A549 Cytotoxicity:	0.382	Hek293 Cytotoxicity:	0.243
BCF:	1.157 ? Bioconcentration factors are used for considering secondary poisoning potential and assessing risks to human health via the food chain. The unit is -log10[(mg/L)/(1000*MW)].	IGC50:	5.2 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	6.508 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	5.49 ? 96 hour fathead minnow LC50. The unit of LC50FM is -log10[(mg/L)/(1000*MW)].

Species Source

Organism ID	Organism Name	Taxonomy Level	Family	SuperKingdom	Isolation Part	Collection Location	Collection Time	Reference
NPO26237	Piper longum	Species	Piperaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[16872768]
NPO26237	Piper longum	Species	Piperaceae	Eukaryota	fruits	n.a.	n.a.	PMID[20839888]
NPO26237	Piper longum	Species	Piperaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[23434420]
NPO26237	Piper longum	Species	Piperaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO26237	Piper longum	Species	Piperaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO26237	Piper longum	Species	Piperaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO26237	Piper longum	Species	Piperaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO26237	Piper longum	Species	Piperaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO26237	Piper longum	Species	Piperaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]

Note for Reference:
In addition to directly collecting NP source organism data from primary literature (where reference will provided as NCBI PMID or DOI links), NPASS also integrated them from below databases:
☉ UNPD: Universal Natural Products Database [PMID: 23638153].
☉ StreptomeDB: a database of streptomycetes natural products [PMID: 33051671].
☉ TM-MC: a database of medicinal materials and chemical compounds in Northeast Asian traditional medicine [PMID: 26156871].
☉ TCM@Taiwan: a Traditional Chinese Medicine database [PMID: 21253603].
☉ TCMID: a Traditional Chinese Medicine database [PMID: 29106634].
☉ TCMSP: The traditional Chinese medicine systems pharmacology database and analysis platform [PMID: 24735618].
☉ HerDing: a herb recommendation system to treat diseases using genes and chemicals [PMID: 26980517].
☉ MetaboLights: a metabolomics database [PMID: 27010336].
☉ FooDB: a database of constituents, chemistry and biology of food species [www.foodb.ca].

NP Quantity Composition/Concentration

Organism ID	Organism Name	Organism Material Preparation	Organism Part	NP Quantity (Standard)	NP Quantity (Minimum)	NP Quantity (Maximum)	Quantity Unit	Reference

Note for Reference:
In addition to directly collecting NP quantitative data from primary literature (where reference will provided as NCBI PMID or DOI links), NPASS also integrated NP quantitative records for specific NP domains (e.g., NPS from foods or herbs) from domain-specific databases. These databases include:
☉ DUKE: Dr. Duke's Phytochemical and Ethnobotanical Databases.
☉ PHENOL EXPLORER: is the first comprehensive database on polyphenol content in foods [PMID: 24103452], its homepage can be accessed at here.
☉ FooDB: a database of constituents, chemistry and biology of food species [www.foodb.ca].

Biological Activity

Activity Type	# Activity
Ratio CC50/IC50	2
IC50	2

Activity Type	# Activity
Organism	2
Others	2

Molecular-level activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference

In vitro activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT963	Organism	Hepatitis B virus	Hepatitis B virus	IC50	=	1070000.0	nM	PMID[23434420]
NPT963	Organism	Hepatitis B virus	Hepatitis B virus	IC50	=	580000.0	nM	PMID[23434420]
NPT2	Others	Unspecified	n.a.	Ratio CC50/IC50	=	1.5	n.a.	PMID[23434420]
NPT2	Others	Unspecified	n.a.	Ratio CC50/IC50	=	2.7	n.a.	PMID[23434420]

In vivo activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference

Experimental ADME

Experiment Model	Experiment Tissue	ADME Type	ADME Relation	ADME Value	ADME Unit	Reference

Experimental Toxicity

Quantitative toxicity

Experiment Model	Experiment Organism	Toxicity Type	Toxicity Relation	Toxicity Value	Toxicity Unit	Reference

Common Abbreviations:
LC: Lethal Concentration; LD: Lethal Dose; LT:Lethal Time; NOAEL: No-observed-adverse-effect Level; BMDL: Benchmark Dose Lower Confidence Limit; BMD: Benchmark Dose; BMC:Benchmark Concentration; LOAEL: Lowest Observed Adverse Effect Level; RfD:Reference Dose; RfC:Reference Concentration; MRL: Minimal Risk Level; MEG: Maximum Exposure Guideline; PAC: Protective Action Criteria

Categorical toxicity labels

Hepatotoxicity	Carcinogenicity	Mutagenicity	Cardiotoxicity	Respiratory Toxicity	Eye Irritation	Endocrine Disruption

Note for Reference:
In addition to directly collecting NP quantitative data from primary literature (where reference will provided as NCBI PMID or DOI links), NPASS also integrated NP toxicity records from domain-specific databases. These databases include:
☉ ToxValDB: a curated database that compiles quantitative toxicity values for chemicals from diverse public sources to support toxicological research and risk assessment.
☉ TOXRIC: a comprehensive, free-to-access, online database providing toxicological/feature data. The toxicity labels are retrieved from this database. [PMID: 36400569]

Chemically structural similarity

Similar Active Natural Products in NPASS

Top-200 similar NPs were calculated against the active-NP-set (includes approximately 50,000 NPs with experimentally-derived bioactivity available in NPASS)

Similarity is measured using the Tanimoto coefficient (Tc) , which compares the binary fingerprints of two molecules. Tc is calculated as the intersection divided by the union of '1' bits in the fingerprints, ranging from 0 to 1, with 1 indicating highest similarity.

● The left chart: Distribution of similarity level between NPC104138 and all remaining natural products in the NPASS database.
● The right table: Most similar natural products (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	36241
0.1-0.2	12479
0.2-0.3	950
0.3-0.4	135
0.4-0.5	23
0.5-0.6	5
0.6-0.7	11
0.7-0.8	0
0.8-0.85	0
0.85-0.9	0
0.9-0.95	1
0.95-1	5

Similarity Score	Similarity Level	Natural Product ID
1.0	High Similarity	NPC273023
1.0	High Similarity	NPC24216
1.0	High Similarity	NPC306420
0.9697	High Similarity	NPC261158
0.9688	High Similarity	NPC195986
0.9118	High Similarity	NPC303672
0.7714	Intermediate Similarity	NPC243539
0.7429	Intermediate Similarity	NPC145032
0.7429	Intermediate Similarity	NPC307435
0.7429	Intermediate Similarity	NPC304223
0.7429	Intermediate Similarity	NPC54542
0.7317	Intermediate Similarity	NPC187315
0.7222	Intermediate Similarity	NPC267340
0.6923	Remote Similarity	NPC312826
0.6585	Remote Similarity	NPC297020
0.6486	Remote Similarity	NPC267692
0.6429	Remote Similarity	NPC119655
0.6429	Remote Similarity	NPC471992
0.6341	Remote Similarity	NPC167759
0.6341	Remote Similarity	NPC56028
0.6341	Remote Similarity	NPC123669
0.619	Remote Similarity	NPC6795
0.6047	Remote Similarity	NPC305288
0.6047	Remote Similarity	NPC163912
0.5581	Remote Similarity	NPC13011
0.5581	Remote Similarity	NPC124382
0.5526	Remote Similarity	NPC245650
0.5172	Remote Similarity	NPC41331
0.5172	Remote Similarity	NPC291449

Similar Clinical/Approved Drugs

Similarity level is defined by Tanimoto coefficient (Tc) between two molecules.

● The left chart: Distribution of similarity level between NPC104138 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	6806
0.1-0.2	2258
0.2-0.3	76
0.3-0.4	10
0.4-0.5	0
0.5-0.6	0
0.6-0.7	0
0.7-0.8	0
0.8-0.85	0
0.85-0.9	0
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Drug ID	Developmental Stage
		NPD

Bioactivity similarity

Similar Natural Products in NPASS

Similarity level is defined by Bioactivity similarity was calculated based on bioactivity descriptors of compounds. The bioactivity descriptors were calculated by a recently developed AI algorithm Chemical Checker (CC) [Nature Biotechnology, 38:1087–1096, 2020; Nature Communications, 12:3932, 2021], which evaluated bioactivity similarities at five levels:
☉ A: chemistry similarity;
☉ B: biological targets similarity;
☉ C: networks similarity;
☉ D: cell-based bioactivity similarity;
☉ E: similarity based on clinical data.
Those 5 categories of CC bioactivity descriptors were calculated and then subjected to manifold projection using UMAP algorithm, to project all NPs on a 2-Dimensional space. The current NP was highlighted with a small circle in the 2-D map. Below figures: left-to-right, A-to-E.

A: chemistry similarity

B: biological targets similarity

C: networks similarity

D: cell-based bioactivity similarity

E: similarity based on clinical data